30204-31-0Relevant articles and documents
Cyclic Analogs of Desferrioxamine e Siderophore for 68Ga Nuclear Imaging: Coordination Chemistry and Biological Activity in Staphylococcus aureus
Decristoforo, Clemens,Gumienna-Kontecka, Elzbieta,Hubmann, Isabella,Koz?owski, Henryk,Krzywik, Julia,Misslinger, Matthias,Mular, Andrzej,Shanzer, Abraham
supporting information, p. 17846 - 17857 (2021/12/01)
As multidrug-resistant bacteria are an emerging problem and threat to humanity, novel strategies for treatment and diagnostics are actively sought. We aim to utilize siderophores, iron-specific strong chelating agents produced by microbes, as gallium ion carriers for diagnosis, applying that Fe(III) can be successfully replaced by Ga(III) without losing biological properties of the investigated complex, which allows molecular imaging by positron emission tomography (PET). Here, we report synthesis, full solution chemistry, thermodynamic characterization, and the preliminary biological evaluation of biomimetic derivatives (FOX) of desferrioxamine E (FOXE) siderophore, radiolabeled with 68Ga for possible applications in PET imaging of S. aureus. From a series of six biomimetic analogs, which differ from FOXE with cycle length and position of hydroxamic and amide groups, the highest Fe(III) and Ga(III) stability was determined for the most FOXE alike compounds-FOX 2-4 and FOX 2-5; we have also established the stability constant of the Ga-FOXE complex. For this purpose, spectroscopic and potentiometric titrations, together with the Fe(III)-Ga(III) competition method, were used. [68Ga]Ga-FOXE derivatives uptake and microbial growth promotion studies conducted on S. aureus were efficient for compounds with a larger cavity, i.e., FOX 2-5, 2-6, and 3-5. Even though showing low uptake values, Fe-FOX 2-4 seems to be also a good Fe-source to support the growth of S. aureus. Overall, proposed derivatives may hold potential as inert and stable carrier agents for radioactive Ga(III) ions for diagnostic medical applications or interesting starting compounds for further modifications.
4-Biphenylalanine- and 3-Phenyltyrosine-Derived Hydroxamic Acids as Inhibitors of the JumonjiC-Domain-Containing Histone Demethylase KDM4A
Morera, Ludovica,Roatsch, Martin,Fürst, Michael C. D.,Hoffmann, Inga,Senger, Johanna,Hau, Mirjam,Franz, Henriette,Schüle, Roland,Heinrich, Markus R.,Jung, Manfred
, p. 2063 - 2083 (2016/10/22)
Overexpression of the histone lysine demethylase KDM4A, which regulates H3K9 and H3K36 methylation states, has been related to the pathology of several human cancers. We found that a previously reported hydroxamate-based histone deacetylase (HDAC) inhibitor (SW55) was also able to weakly inhibit this demethylase with an IC50value of 25.4 μm. Herein we report the synthesis and biochemical evaluations, with two orthogonal in vitro assays, of a series of derivatives of this lead structure. With extensive chemical modifications on the lead structure, also by exploiting the versatility of the radical arylation with aryldiazonium salts, we were able to increase the potency of the derivatives against KDM4A to the low-micromolar range and, more importantly, to obtain demethylase selectivity with respect to HDACs. Cell-permeable derivatives clearly showed a demethylase-inhibition-dependent antiproliferative effect against HL-60 human promyelocytic leukemia cells.
Hydroxamic acid derivative and JHDM inhibitor
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Paragraph 0039; 0127, (2016/10/09)
PROBLEM TO BE SOLVED: To provide a compound capable of selectively inhibiting the function of JHDM, and a JHDM inhibitor. SOLUTION: This hydroxamic acid derivative expressed by formula (1a) [wherein, R1and R2are each independently alkyl which may have a branch; and (n) is an integer of ≥1] or general formula (1b) [wherein, ring X is a 3 to 8-membered saturated carbon ring; and (n) is an integer of ≥1], its pharmaceutically acceptable salt, hydrate, solvate or prodrug is provided. COPYRIGHT: (C)2011,JPOandINPIT
Identification of the KDM2/7 histone lysine demethylase subfamily inhibitor and its antiproliferative activity
Suzuki, Takayoshi,Ozasa, Hiroki,Itoh, Yukihiro,Zhan, Peng,Sawada, Hideyuki,Mino, Koshiki,Walport, Louise,Ohkubo, Rei,Kawamura, Akane,Yonezawa, Masato,Tsukada, Yuichi,Tumber, Anthony,Nakagawa, Hidehiko,Hasegawa, Makoto,Sasaki, Ryuzo,Mizukami, Tamio,Schofield, Christopher J.,Miyata, Naoki
, p. 7222 - 7231 (2013/10/21)
Histone Nε-methyl lysine demethylases KDM2/7 have been identified as potential targets for cancer therapies. On the basis of the crystal structure of KDM7B, we designed and prepared a series of hydroxamate analogues bearing an alkyl chain. Enzyme assays revealed that compound 9 potently inhibits KDM2A, KDM7A, and KDM7B, with IC50s of 6.8, 0.2, and 1.2 μM, respectively. While inhibitors of KDM4s did not show any effect on cancer cells tested, the KDM2/7-subfamily inhibitor 9 exerted antiproliferative activity, indicating the potential for KDM2/7 inhibitors as anticancer agents.
Design, synthesis, enzyme-inhibitory activity, and effect on human cancer cells of a novel series of jumonji domain-containing protein 2 histone demethylase inhibitors
Hamada, Shohei,Suzuki, Takayoshi,Mino, Koshiki,Koseki, Koichi,Oehme, Felix,Flamme, Ingo,Ozasa, Hiroki,Itoh, Yukihiro,Ogasawara, Daisuke,Komaarashi, Haruka,Kato, Aiko,Tsumoto, Hiroki,Nakagawa, Hidehiko,Hasegawa, Makoto,Sasaki, Ryuzo,Mizukami, Tamio,Miyata, Naoki
experimental part, p. 5629 - 5638 (2010/10/03)
Selective inhibitors of Jumonji domain-containing protein (JMJD) histone demethylases are candidate anticancer agents as well as potential tools for elucidating the biological functions of JMJDs. On the basis of the crystal structure of JMJD2A and a homology model of JMJD2C, we designed and prepared a series of hydroxamate analogues bearing a tertiary amine. Enzyme assays using JMJD2C, JMJD2A, and prolyl hydroxylases revealed that hydroxamate analogue 8 is a potent and selective JMJD2 inhibitor, showing 500-fold greater JMJD2C-inhibitory activity and more than 9100-fold greater JMJD2C-selectivity compared with the lead compound N-oxalylglycine 2. Compounds 17 and 18, prodrugs of compound 8, each showed synergistic growth inhibition of cancer cells in combination with an inhibitor of lysine-specific demethylase 1 (LSD1). These findings suggest that combination treatment with JMJD2 inhibitors and LSD1 inhibitors may represent a novel strategy for anticancer chemotherapy.
Studies towards the biomimetic synthesis of pyridomacrolidin
Irlapati, Nageswara Rao,Baldwin, Jack E.,Adlington, Robert M.,Pritchard, Gareth J.,Cowley, Andrew R.
, p. 4603 - 4614 (2007/10/03)
A possible biomimetic synthesis of pyridomacrolidin has been proposed and experimentally supported by carrying out a model study. Regio and stereospecific [3+2] cycloaddition of an in situ generated unusual di-tert-butylated acyl nitrone with Z-2-cyclodecenone and subsequent aromatisation was the key step in our proposed biomimetic synthesis. Finally a pyridomacrolidin analogue was prepared via Friedel-Crafts di-de-t-butylation of the cycloadduct.
An unusual oxidative cyclization: Studies towards the biomimetic synthesis of pyridomacrolidin
Irlapati, Nageswara Rao,Baldwin, Jack E.,Adlington, Robert M.,Pritchard, Gareth J.,Cowley, Andrew
, p. 2351 - 2354 (2007/10/03)
(Matrix presented) An unusual oxidative cyclization of a N-hydroxy pyridone 9 with Z-2-cyclodecenone 11 has been achieved, thus demonstrating a possible biomimetic route to pyridomacrolidin 2.
